Antibiotics Off the Beaten Path

As more antibiotic-resistant “superbugs” emerge, it’s clear that we desperately need new antimicrobial drugs. Yet, over the past couple of decades, antibiotic discovery has largely been stagnant.

“The reality is there’s almost no new antibiotics that are developed. And that’s because pharmaceutical companies have decreased their investment—in part because of the rediscovery issue,” explains bacteriology professor Cameron Currie.

The “rediscovery issue” refers to the fact that soil has historically been the prime source of new antibiotics—but it seems to be tapped out. When scientists screen soil microbes for new antibiotics, they keep finding the same compounds over and over again.

Currie is part of a team that is looking elsewhere.

Currie and his colleagues have been focusing their efforts on microbes that are associated with insects, plants and marine life from all around the United States, funded by a $16 million grant from the National Institutes of Health that was awarded in 2014.

“One of the major hurdles is finding new compounds, and that’s where we’re really excelling,” says Currie, a co-principal investigator on the grant. His partner is David Andes in the UW–Madison School of Medicine and Public Health.

At the front end, the work involves some good old-fashioned bioprospecting. Currie’s group, which is in charge of the terrestrial sphere, has gathered more than 2,000 flies, aphids, caterpillars, bees, ants and other insects, as well as mushrooms and plants, from locales near and far, including Alaska, Hawaii and Wisconsin’s Devil’s Lake.

Back at the lab, things get high-tech pretty quickly. Microbes are isolated from the samples and tested for antimicrobial activity. Promising strains undergo genetic sequencing that allows Currie’s group to determine how likely they are to produce novel antibiotic compounds. From there, other scientists involved in the grant go on to test the most promising compounds in a mouse model of infection. This approach has already yielded some exciting drug candidates.

“We have 9,000 strains to screen, and we have already found some new compounds that are effective at combating infections in mice and have low toxicity,” says Currie.

With so many samples to process, Currie’s group adopted bar code technology to help them keep track. They have a bar code reader—like you’d find in a grocery store— connected to a lab computer that they use to scan petri dishes, look up samples and add new data. For each microbial strain they’ve isolated, the database has photos of the “host” insect or plant, GPS coordinates for the collection site, assay results, genetic sequence and much more.

At this point, Currie feels confident that the project will pay off, and he’s eager to see one of the group’s compounds go into human clinical trials.

“If you find one new antibiotic that gets used in treatment, it’s a major success. You’re saving people’s lives,” Currie says.

The MBA of Dairy

The average age of a Wisconsin farmer is over 56 and rising, and the state has been losing around 500 dairy farms per year. It’s no surprise, then, that experts say it’s critical to prepare young people to step into farm roles in order to keep the state’s $88 billion agricultural economy strong into the future.

But making the transition into dairy farming is complicated, and aspiring farmers often don’t have the capital or the experience to take over an established operation.

Enter the Dairy Grazing Apprenticeship (DGA) program, which is working to address the issue by providing support for young people interested in becoming dairy farmers. Started in 2010, the first-of-its-kind program is administered by the Wisconsin-based nonprofit GrassWorks, Inc., with CALS as a key partner.

Earlier this year, DGA received $750,000 from the U.S. Department of Agriculture’s Beginning Farmer and Rancher Development Program. The funding will enable organizers to improve and expand the program in Wisconsin, as well as explore the possibility of rolling it out to other dairy states.

“It’s a meat-and-potatoes program that really takes people up to the level where they can own and operate their own dairy,” says DGA director Joe Tomandl. “It’s the MBA of dairy.”

Program participants complete 4,000 hours of paid training over two years, most of it alongside experienced dairy farmers, and work their way up from apprentices to Journey Dairy Graziers and Master Dairy Graziers. Although most of that time is spent in on-the-job training, there’s also a significant requirement for related instruction. That’s where CALS comes in.

As part of the program, apprentices attend a seminar about pasture-based dairy and livestock through the Wisconsin School for Beginning Dairy and Livestock Farmers (WSBDF), which is co-sponsored by the CALS-based Center for Integrated Agricultural Systems and the Farm and Industry Short Course. The seminar involves a 32-hour commitment, which is generally fulfilled through distance education and includes instruction from CALS professors from dairy, animal and soil sciences.

“We believe in the Wisconsin Idea and want to make sure our classes are accessible to people who want more education, but preferably close to where they live and work,” says Nadia Alber, a WSBDF outreach coordinator who helps organize the seminar and also serves on the DGA board.

In 2009, GrassWorks, Inc. turned to WSBDF director Dick Cates PhD’83 for guidance and access to a well-respected educational curriculum to help get the DGA up and running—and the WSBDF team has been involved ever since.

“We were just this little nonprofit with a very small budget trying to compete for a big federal grant,” says Tomandl. “For us, it was important to have UW–Madison as a strategic partner.”

As part of the most recent round of funding, DGA’s partners at CALS will lead an effort to quantify the program’s broader impacts.
“They have already proven that participants are moving along to their own farms after the apprenticeship, so they have an established track record,” says Alber. “This new study will look at some of the program’s other impacts, including economic, environmental and social.”

Plant Prowess

It may look jury-rigged, but it’s cutting-edge science.

In a back room in the university’s Seeds Building, researchers scan ears of corn—three at a time—on a flatbed scanner, the kind you’d find at any office supply store. After running the ears through a shelling machine, they image the de-kerneled cobs on a second scanner.

The resulting image files—up to 40 gigabytes’ worth per day—are then run through a custom-made software program that outputs an array of yield-related data for each individual ear. Ultimately, the scientists hope to link this type of information—along with lots of other descriptive data about how the plants grow and what they look like—back to the genes that govern those physical traits. It’s part of a massive national effort to deliver on the promise of the corn genome, which was sequenced back in 2009, and help speed the plant breeding process for this widely grown crop.

“When it comes to crop improvement, the genotype is more or less useless without attaching it to performance,” explains Bill Tracy, professor and chair of the Department of Agronomy. “The big thing is phenotyping—getting an accurate and useful description of the organism—and connecting that information back to specific genes. It’s the biggest thing in our area of plant sciences right now, and we as a college are playing a big role in that.”

No surprise there. Since the college’s founding, plant scientists at CALS have been tackling some of the biggest issues of their day. Established in 1889 to help fulfill the University of Wisconsin’s land grant mission, the college focused on supporting the state’s fledgling farmers, helping them figure out how to grow crops and make a living at it. At the same time, this practical assistance almost always included a more basic research component, as researchers sought to understand the underlying biology, chemistry and physics of agricultural problems.

That approach continues to this day, with CALS plant scientists working to address the ever-evolving agricultural and natural resource challenges facing the state, the nation and the world. Taken together, this group constitutes a research powerhouse, with members based in almost half of the college’s departments, including agronomy, bacteriology, biochemistry, entomology, forest and wildlife ecology, genetics, horticulture, plant pathology and soil science.

“One of our big strengths here is that we span the complete breadth of the plant sciences,” notes Rick Lindroth, associate dean for research at CALS and a professor of entomology. “We have expertise across the full spectrum—from laboratory to field, from molecules to ecosystems.”

This puts the college in the exciting position of tackling some of the most complex and important issues of our time, including those on the applied science front, the basic science front—and at the exciting new interface where the two approaches are starting to intersect, such as the corn phenotyping project.

“The tools of genomics, informatics and computation are creating unprecedented opportunities to investigate and improve plants for humans, livestock and the natural world,” says Lindroth. “With our historic strength in both basic and applied plant sciences, the college is well positioned to help lead the nation at this scientific frontier.”

It’s hard to imagine what Wisconsin’s agricultural economy would look like today without the assistance of CALS’ applied plant scientists.

The college’s early horticulturalists helped the first generation of cranberry growers turn a wild bog berry into an economic crop. Pioneering plant pathologists identified devastating diseases in cabbage and potato, and then developed new disease-resistant varieties. CALS agronomists led the development of the key forage crops—including alfalfa and corn—that feed our state’s dairy cows.

Fast-forward to 2015: Wisconsin is the top producer of cranberries, is third in the nation in potatoes and has become America’s Dairyland. And CALS continues to serve the state’s agricultural industry.

The college’s robust program covers a wide variety of crops and cropping systems, with researchers addressing issues of disease, insect and weed control; water and soil conservation; nutrient management; crop rotation and more. The college is also home to a dozen public plant-breeding programs—for sweet corn, beet, carrot, onion, potato, cranberry, cucumber, melon, bean, pepper, squash, field corn and oats—that have produced scores of valuable new varieties over the years, including a number of “home runs” such as the Snowden potato, a popular potato chip variety, and the HyRed cranberry, a fast-ripening berry designed for Wisconsin’s short growing season.

While CALS plant scientists do this work, they also train the next generation of researchers—lots of them. The college’s Plant Breeding and Plant Genetics Program, with faculty from nine departments, has trained more graduate students than any other such program in the nation. Just this past fall, the Biology Major launched a new plant biology option in response to growing interest among undergraduates.

“If you go to any major seed company, you’ll find people in the very top leadership positions who were students here in our plant-breeding program,” says Irwin Goldman PhD’91, professor and chair of the Department of Horticulture.

Among the college’s longstanding partnerships, CALS’ relationship with the state’s potato growers is particularly strong, with generations of potato growers working alongside generations of CALS scientists. The Wisconsin Potato and Vegetable Growers Association (WPVGA), the commodity group that supports the industry, spends more than $300,000 on CALS-led research each year, and the group helped fund the professorship that brought Jeff Endelman, a national leader in statistical genetics, to campus in 2013 to lead the university’s potato-breeding program.

“Research is the watchword of the Wisconsin potato and vegetable industry,” says Tamas Houlihan, executive director of the WPVGA. “We enjoy a strong partnership with CALS researchers in an ongoing effort to solve problems and improve crops, all with the goal of enhancing the economic vitality of Wisconsin farmers.”

Over the decades, multi-disciplinary teams of CALS experts have coalesced around certain crops, including potato, pooling their expertise.

“Once you get this kind of core group working, it allows you to do really high-impact work,” notes Patty McManus, professor and chair of the Department of Plant Pathology and a UW–Extension fruit crops specialist.

CALS’ prowess in potato, for instance, helped the college land a five-year, $7.6 million grant from the U.S. Department of Agriculture to help reduce levels of acrylamide, a potential carcinogen, in French fries and potato chips. The multistate project involves plant breeders developing new lines of potato that contain lower amounts of reducing sugars (glucose and fructose) and asparagine, which combine to form acrylamide when potatoes are fried. More than a handful of conventionally bred, low-acrylamide potato varieties are expected to be ready for commercial evaluations within a couple of growing seasons.

“It’s a national effort,” says project manager Paul Bethke, associate professor of horticulture and USDA-ARS plant physiologist. “And by its nature, there’s a lot of cross-talk between the scientists and the industry.”

Working with industry and other partners, CALS researchers are responding to other emerging trends, including the growing interest in sustainable agricultural systems.

“Maybe 50 years ago, people focused solely on yield, but that’s not the way people think anymore. Our crop production people cannot just think about crop production, they have to think about agroecology, about sustainability,” notes Tracy. “Every faculty member doing production research in the agronomy department, I believe, has done some kind of organic research at one time or another.”

Embracing this new focus, over the past two years CALS has hired two new assistant professors—Erin Silva, in plant pathology, who has responsibilities in organic agriculture, and Julie Dawson, in horticulture, who specializes in urban and regional food systems.

“We still have strong partnerships with the commodity groups, the cranberries, the potatoes, but we’ve also started serving a new clientele—the people in urban agriculture and organics that weren’t on the scene for us 30 years ago,” says Goldman. “So we have a lot of longtime partners, and then some new ones, too.”

Working alongside their applied colleagues, the college’s basic plant scientists have engaged in parallel efforts to reveal fundamental truths about plant biology—truths that often underpin future advances on the applied side of things.

For example, a team led by Aurélie Rakotondrafara, an assistant professor of plant pathology, recently found a genetic element—a stretch of genetic code—in an RNA-based plant virus that has a very useful property. The element, known as an internal ribosome entry site, or IRES, functions like a “landing pad” for the type of cellular machine that turns genes—once they’ve been encoded in RNA—into proteins. (A Biology 101 refresher: DNA—>RNA—>Protein.)

This viral element, when harnessed as a tool of biotechnology, has the power to transform the way scientists do their work, allowing them to bypass a longstanding roadblock faced by plant researchers.

“Under the traditional mechanism of translation, one RNA codes for one protein,” explains Rakotondrafara. “With this IRES, however, we will be able to express several proteins at once from the same RNA.”

Rakotondrafara’s discovery, which won an Innovation Award from the Wisconsin Alumni Research Foundation (WARF) this past fall and is in the process of being patented, opens new doors for basic researchers, and it could also be a boon for biotech companies that want to produce biopharmaceuticals, including multicomponent drug cocktails, from plants.

Already, Rakotondrafara is working with Madison-based PhylloTech LLC to see if her new IRES can improve the company’s tobacco plant-based biofarming system.

“The idea is to produce the proteins we need from plants,” says Jennifer Gottwald, a technology officer at WARF. “There hasn’t been a good way to do this before, and Rakotondrafara’s discovery could actually get this over the hump and make it work.”

While Rakotondrafara is a basic scientist whose research happened to yield a powerful application, CALS has a growing number of scientists—including those involved in the corn phenotyping project—who are working at the exciting new interface where basic and applied research overlap. This new space, created through the mind-boggling advances in genomics, informatics and computation made in recent years, is home to an emerging scientific field where genetic information and other forms of “big data” will soon be used to guide in-the-field plant-breeding efforts.

Sequencing the genome of an organism, for instance, “is almost trivial in both cost and difficulty now,” notes agronomy’s Bill Tracy. But a genome—or even a set of 1,000 genomes—is only so helpful.

What plant scientists and farmers want is the ability to link the genetic information inside different corn varieties—that is, the activity of specific genes inside various corn plants—to particular plant traits observed in the greenhouse or the field. The work of chronicling these traits, known as phenotyping, is complex because plants behave differently in different environments—for instance, growing taller in some regions and shorter in others.

“That’s one of the things that the de Leon and Kaeppler labs are now moving their focus to—massive phenotyping. They’ve been doing it for a while, but they’re really ramping up now,” says Tracy, referring to agronomy faculty members Natalia de Leon MS’00 PhD’02 and Shawn Kaeppler.

After receiving a large grant from the Great Lakes Bioenergy Research Center in 2007, de Leon and Kaeppler decided to integrate their two research programs. They haven’t looked back. With de Leon’s more applied background in plant breeding and field evaluation, plus quantitative genetics, and with Kaeppler’s more basic corn genetics expertise, the two complement each other well. The duo have had great success securing funding for their various projects from agencies including the National Science Foundation, the U.S. Department of Agriculture and the U.S. Department of Energy.

“A lot of our focus has been on biofuel traits, but we measure other types of economically valuable traits as well, such as yield, drought tolerance, cold tolerance and others,” says Kaeppler. Part of the work involves collaborating with bioinformatics experts to develop advanced imaging technologies to quantify plant traits, projects that can involve assessing hundreds of plants at a time using tools such as lasers, drone-mounted cameras and hyperspectral cameras.

This work requires a lot of space to grow and evaluate plants, including greenhouse space with reliable climate control in which scientists can precisely measure the effects of environmental conditions on plant growth. That space, however, is in short supply on campus.

“A number of our researchers have multimillion-dollar grants that require thousands of plants to be grown, and we don’t always have the capacity for it,” says Goldman.

That’s because the Walnut Street Greenhouses, the main research greenhouses on campus, are already packed to the gills with potato plants, corn plants, cranberries, cucumbers, beans, alfalfa and dozens of other plant types. At any given moment, the facility has around 120 research projects under way, led by 50 or so different faculty members from across campus.

Another bottleneck is that half of the greenhouse space at Walnut Street is old and sorely outdated. The facility’s newer greenhouses, built in 2005, feature automated climate control, with overlapping systems of fans, vents, air conditioners and heaters that help maintain a pre-set temperature. The older houses, constructed of single-pane glass, date back to the early 1960s and present a number of challenges to run and maintain. Some don’t even have air conditioning—the existing electrical system can’t handle it. Temperatures in those houses can spike to more than 100 degrees during the summer.

“Most researchers need to keep their plants under fairly specific and constant conditions,” notes horticultural technician Deena Patterson. “So the new section greenhouse space is in much higher demand, as it provides the reliability that good research requires.”

To help ameliorate the situation, the college is gearing up to demolish the old structures and expand the newer structure, adding five more wings of greenhouse rooms, just slightly north of the current location—out from under the shadow of the cooling tower of the West Campus Co-Generation Facility power plant, which went online in 2005. The project, which will be funded through a combination of state and private money, is one of the university’s top building priorities.

Fortunately, despite the existing limitations, the college’s plant sciences research enterprise continues apace. Kaeppler and de Leon, for example, are involved in an exciting phenotyping project known as Genomes to Fields, which is being championed by corn grower groups around the nation. These same groups helped jump-start an earlier federal effort to sequence the genomes of many important plants, including corn.

“Now they’re pushing for the next step, which is taking that sequence and turning it into products,” says Kaeppler. “They are providing initial funding to try to grow Genomes to Fields into a big, federally funded initiative, similar to the sequencing project.”

It’s a massive undertaking. Over 1,000 different varieties of corn are being grown and evaluated in 22 environments across 13 states and one Canadian province. Scientists from more than a dozen institutions are involved, gathering traditional information about yield, plant height and flowering times, as well as more complex phenotypic information generated through advanced imaging technologies. To this mountain of data, they add each corn plant’s unique genetic sequence.

“You take all of this data and just run millions and billions of associations for all of these different traits and genotypes,” says de Leon, who is a co-principal investigator on the project. “Then you start needing supercomputers.”

Once all of the dots are connected—when scientists understand how each individual gene impacts plant growth under various environmental conditions—the process of plant breeding will enter a new sphere.

“The idea is that instead of having to wait for a corn plant to grow for five months to measure a certain trait out in the field, we can now take DNA from the leaves of little corn seedlings, genotype them and make decisions within a couple of weeks regarding which ones to advance and which to discard,” says de Leon. “The challenge now is how to be able to make those types of predictions across many environments, including some that we have never measured before.”

To get to that point, notes de Leon, a lot more phenotypic information still needs to be collected—including hundreds and perhaps thousands more images of corn ears and cobs taken using flatbed scanners.

“Our enhanced understanding of how all of these traits are genetically controlled under variable environmental conditions allows us to continue to increase the efficiency of plant improvement to help meet the feed, food and fiber needs of the world’s growing population,” she says.

Sidebar:

The Bigger Picture

Crop breeders aren’t the only scientists doing large-scale phenotyping work. Ecologists, too, are increasingly using that approach to identify the genetic factors that impact the lives of plants, as well as shape the effects of plants on their natural surroundings.

“Scientists are starting to look at how particular genes in dominant organisms in an environment—often trees—eventually shape how the ecosystem functions,” says entomology professor Rick Lindroth, who also serves as CALS’ associate dean for research. “Certain key genes are driving many fantastically interesting and important community- and ecosystem-level interactions.”

How can tree genes have such broad impacts? Scientists are discovering that the answer, in many cases, lies in plant chemistry.
“A tree’s chemical composition, which is largely determined by its genes, affects the community of insects that live on it, and also the birds that visit to eat the insects,” explains Lindroth. “Similarly, chemicals in a tree’s leaves affect the quality of the leaf litter on the ground below it, impacting nutrient cycling and nitrogen availability in nearby soils.”

A number of years ago Lindroth’s team embarked on a long-term “genes-to-ecosystems” project (as these kinds of studies are called) involving aspen trees. They scoured the Wisconsin landscape, collecting root samples from 500 different aspens. From each sample, they propagated three or four baby trees, and then in 2010 planted all 1,800 saplings in a so-called “common garden” at the CALS-based Arlington Agricultural Research Station.

“The way a common garden works is, you put many genetic strains of a single species in a similar environment. If phenotypic differences are expressed within the group, then the likelihood is that those differences are due to their genetics, not the environment,” explains Lindroth.

Now that the trees have had some time to grow, Lindroth’s team has started gathering data about each tree—information such as bud break, bud set, tree size, leaf shape, leaf chemistry, numbers and types of bugs on the trees, and more.

Lindroth and his partners will soon have access to the genetic sequence of all 500 aspen genetic types. Graduate student Hilary Bultman and postdoctoral researcher Jennifer Riehl will do the advanced statistical analysis involved—number crunching that will reveal which genes underlie the phenotypic differences they see.

In this and in other projects, Lindroth has called upon the expertise of colleagues across campus, developing strategic collaborations as needed. That’s easy to do at UW–Madison, notes Lindroth, where there are world-class plant scientists working across the full spectrum of the natural resources field—from tree physiology to carbon cycling to climate change.

“That’s the beauty of being at a place like Wisconsin,” Lindroth says.

Want to help? The college welcomes your gift toward modernizing the Walnut Street Greenhouses. To donate, please visit: supportuw.org/giveto/WalnutGreenhouse. We thank you for your contribution.
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From Trash to Treasure

CDR food technologist Dean Sommers showing a beaker of acid whey. The high-tech filters used to separate the various components are inside the metal pipes.

CDR food technologist Dean Sommers showing a beaker of acid whey. The high-tech filters used to separate the various components are inside the metal pipes.

With exploding consumer demand for Greek yogurt, production is up. That’s great for food companies’ bottom lines, but it also leaves them dealing with a lot more acid whey, a problematic by-product of the Greek yogurt-making process.

Acid whey, if not properly disposed of, can cause environmental problems. Currently, companies typically pay to landspread it on farmers’ fields or dump it down the drain. Where the option is available, some plants are starting to send it to anaerobic digesters, where it’s fermented to produce methane.

But scientists at the CALS-based Wisconsin Center for Dairy Research (CDR) are developing a better option, one that will transform this trash into treasure.

“The whole goal is to take this problematic mixture of stuff—acid whey—and isolate all of the various components and find commercial uses for them,” says Dean Sommer, a CDR food technologist.

That’s no easy task.

Food companies have been fractionating the components of sweet whey—the by-product of cheese production—for more than a decade now, extracting high-value whey protein powders that are featured in muscle-building products and other high-protein foods and beverages.

Compared to sweet whey, however, acid whey from Greek yogurt is hard to work with. Similar to sweet whey, it’s mostly water—95 percent—but it contains a lot less protein, which is considered the valuable part. Some of the other “solids” in acid whey, which include lactose, lactic acid, calcium, phosphorus and galactose, make it more difficult to process. For instance, thanks to galactose and lactic acid, it turns into a sticky mess when it’s dried down.

Instead of drying it, CDR scientists are developing technologies that utilize high-tech filters, or membranes, to separate out the various components.

“We’re taking the membranes that are available to us and stringing them together and developing a process that allows us to get some value-added ingredients out at the other end,” says dairy processing technologist Karen Smith, who is working on the project.

At this point, the CDR has set its sights on lactose, an ingredient that food companies will pay good money for in food-grade form.

“It’s the lowest-hanging fruit, the most valuable thing in there in terms of volume and potential worth,” says Sommer.

The technology is quite far along. While Sommer can’t divulge names, a number of companies are already implementing lactose-isolating technology in their commercial plants.

Isolating the other components will come later, part of the long-term vision for this technology. When it’s perfected, explains Sommer, acid whey will be stripped of its ingredients until there’s nothing left. “It will just be water,” he says.

Russia: Monitoring Russia’s “rewilding”

Doing fieldwork in the remote wilderness of Russia isn’t for the faint of heart. There are long distances to travel on deeply rutted roads, bleak outpost towns with meager accommodations, and bears and wolves to contend with. Plus—in the case of visiting American scientists—the constant presence of an armed guard who wasn’t there to protect them from large carnivores. “

He was there in case we encountered illegal poachers,” explains forest and wildlife ecology (FWE) professor Volker Radeloff, who has been visiting Russia in a research capacity for a dozen years, most recently with his fellow FWE professor Anna Pidgeon.

According to the duo (who are married), the opportunity to visit two of Russia’s protected areas— the Kologrivksi Forest northeast of Moscow and the Caucasus Mountains in the south—is worth the trouble.

That’s because Russia offers a unique case study for conservation scientists interested in studying the impact of land use changes on wildlife populations. After the fall of the Soviet Union, citizens abandoned the state’s collectivized farms, leaving many of the agricultural fields to revert to a more natural state—and opening up new space for animals to live and roam.

“Their forests are regrowing and their wildlands are coming back, which is something we don’t see in many other places on the planet—especially at that magnitude,” says Radeloff.

Radeloff, an expert in using satellite imagery to monitor land use changes, can look at his remote sensing data and see that forests are expanding in Russia. But the images don’t tell Radeloff and Pidgeon much about what’s happening “on the ground” with local wildlife populations. For that, they need to partner with Russian scientists, working with them on their turf.

As an example, while satellite imagery can help identify promising habitat for the reintroduction of European bison into new areas within the Caucasus Mountains, many other factors will determine a herd’s ultimate success.

“We identified an area that looked like good habitat, but the local scientists made it quite clear that this would not work because of the human context,” says Radeloff. “They told us the bison would all be shot there within a week; they’d never survive. That’s the kind of information we need that we cannot learn remotely and that nobody is publishing about in scientific journals.”

That “human context” is a significant factor, even within the nation’s protected areas. Animals are hunted for food by locals and for trophies by affluent sportsmen. In the southern Caucasus Mountains, ibex, a type of wild goat, are killed for their horns, which are used as wineglasses during traditional Georgian wedding ceremonies. The Saiga antelope of the Kalmykia are likewise poached for their horns, which are sold on the Chinese medicine market. These forces must be factored in.

Trips to Russia also enable Radeloff and Pidgeon to develop important scientific relationships. They regularly host Russian conservation scientists in their Madison labs, giving visitors the opportunity to work on short projects that can aid their efforts back home in Russia.

“Both of us are interested in capacity building, particularly in countries where the resources or training may not be quite as comprehensive as it is here in the United States,” says Pidgeon. “These relationships lead to a cross-pollination that benefits both sides as we work to study and support wildlife populations in Russia.”

Costa Rica: New trail in paradise

This past January a group of CALS students found themselves bushwhacking through a dense mountain forest in Costa Rica, crossing paths with monkeys, colorful birds, snakes and strange-looking frogs along the way.

But no worries: They weren’t lost.

As part of a service-learning course offered by the Department of Landscape Architecture, they were scouting out a new hiking trail for the Cloud Forest School, a bilingual, environmentally focused K–11 school located just outside the majestic, fog-shrouded cloud forest reserves of Monteverde and Santa Elena. The reserves are among the most biologically diverse places on Earth, serving as home to more than 2,500 plant species, 400 kinds of birds, more than 200 species of mammals, reptiles and amphibians—and thousands of insects.

“We hiked through the most wild parts of the mountain to collect GPS points of potential new trails,” says Lyn Kim, a landscape architecture senior who spent two weeks in Costa Rica as part of the Cloud Forest Studio course, as it’s called.

CALS students helped plan, map and build a five-kilometer trail through the school’s extensive grounds, which include both pristine and previously harvested cloud forest. The path, which includes resting points of special ecological interest, was designed for Cloud Forest School field trips as well as for the school’s annual fundraiser run. Creating it, however, was just one piece of a much larger effort.

“The long-term goal is to help develop some kind of meaningful forest restoration plan for the property,” says landscape architecture professor Sam Dennis, who co-leads the course along with department chair and professor John Harrington.

“We also want to help support the school’s environmental education efforts so their students can go on to jobs in the local ecotourism industry,” he adds.

Dennis and Harrington made a five-year commit- ment to the school and so far have led two groups of CALS students to conduct work there. In addition to building the trail, students have also started develop- ing classroom curriculum materials, nature guides for the property and interpretive trail signage.

The trips expose CALS students to landscape architecture’s vocational variety. “People tend to think of landscape architecture as putting plants onto landscapes, but that’s very little of what we actually do,” explains Harrington. The course gives students
a taste of environmental restoration work, commu- nity development work, and the creation of outdoor educational spaces with community input.

Kim, for one, was thrilled with her experience last January, and not just because she got to see an active volcano and zipline down the side of a mountain on her day off.

“At school we always design on trace paper and in the computer, but we never get to see our designs built,” she notes. “During our trail-building project, we got to see our work come to life.”

Made for the Shade

With the global population expected to reach 9 billion by 2050, the world’s farmers are going to need to produce a lot more food—but without using much more farmland, as the vast majority of the world’s arable land is already being used for agriculture.

One possible solution is to try to grow crops more densely in the field, thereby increasing yield per acre. But it’s not as easy as just spacing seeds more closely together at planting time.

Packed too tight, for instance, corn plants will grow tall and spindly as they try to outcompete neighboring plants for access to sunlight—a phenomenon known as shade avoidance.

“The problem with shade avoidance when it comes to food crops is that the plants are spending all this time and energy making stems so they can grow tall instead of making food that we eat,” explains CALS plant geneticist Richard Vierstra, who is developing a way around it. His team is reengineering a light-sensing molecule found in plants, known as phytochrome, to allow plants to grow normally even when they’re packed in tight.

“Instead of 30-inch rows, this technology could enable us to plant corn in 20-inch rows, boosting yields by as much as 50 percent—if we can get the plants to ignore their neighbors,” says Vierstra.

Phytochrome is the main photoreceptor that allows plants to tell when the lights are on and when they’re off. It’s what tells seeds to germinate and young seedlings to become green, and enables plants to establish circadian rhythms—an internal clock system, says Vierstra. “And it also allows a plant to sense whether it’s in full sun or whether it’s being shaded by other plants.”

In the lab, Vierstra and his team developed the first three-dimensional structures of phytochromes. Using these models, they are now trying to rationally redesign the photoreceptor to have altered light-sensing properties. This reengineering involves creating hundreds of possibly interesting phytochrome mutants, and then testing them for light sensitivity both in the test tube and inside plants.

Already Vierstra’s team has found a number of mutants that are extremely sensitive to light. These mutant phytochrome molecules, if genetically engineered into food crops, could trick the plants into thinking they are getting plenty of light, even when they’re growing in a crowded field.

Vierstra is in the process of patenting the technology and already knows of a large agribusiness company that’s eager to help commercialize it.

“We’re starting to engineer the phytochrome system in corn, in lines that will eventually be used for breeding,” he says. “It’s exciting to think about the potential this technology has to boost agricultural productivity.”

“Open Source” Seeds for All

Scientists, farmers and sustainable food systems advocates recently celebrated the release of 29 new varieties of broccoli, celery, kale and other vegetables and grains that have something unusual in common: a new form of ownership agreement known as the Open Source Seed Pledge.

The pledge, developed through a nationwide effort called the Open Source Seed Initiative, is designed to keep the new seeds free for all people to grow, breed and share for perpetuity, with the goal of protecting the plants from patents and other restrictions.

CALS professors Irwin Goldman (horticulture) and Jack Kloppenburg (community and environmental sociology) have been leaders in the initiative, which arose in response to the decreasing availability of plant germplasm—seeds—for public plant breeders and farmer-breeders to work with.

Many of the seeds for our nation’s big crop plants—field corn and soybeans—are already restricted through patents and licenses. Increasingly this is happening to vegetable, fruit and small grain seeds.

Goldman, who breeds beets, carrots and onions, still plans to license many of his new varieties as usual through the Wisconsin Alumni Research Foundation (WARF), which has been supportive of his interest in open source seeds. But he’s pleased he now has an alternative for when he wants to share new varieties with fellow public plant breeders or small seed companies.

“These vegetables are part of our common cultural heritage, and our goal is to make sure these seeds remain in the public domain for people to use in the future,” he says.

Stopping Multiple Sclerosis

A diagnosis of multiple sclerosis (MS) is a hard lot. Patients typically get the diagnosis around age 30 after experiencing a series of neurological problems such as blurry vision, a wobbly gait or a numb foot.

From there, this neurodegenerative disease follows an unforgiving course. People with severe cases are typically bed-bound by age 60. Current medications don’t do much to slow the disease, which afflicts around 400,000 people nationwide, with 200 new cases diagnosed each week.

Now a team of CALS biochemists has discovered a promising vitamin D–based treatment that can halt—and even reverse—the course of the disease in a mouse model of MS. The treatment involves giving mice exhibiting MS symptoms a single dose of calcitriol, the active hormone form of vitamin D, followed by ongoing vitamin D supplements in their diet.

“All of the animals just got better and better, and the longer we watched them, the more neurological function they regained,” says CALS biochemistry professor Colleen Hayes, who led the study and published her team’s findings in the Journal of Neuroimmunology.

While scientists don’t fully understand what triggers MS, some studies have linked low levels of vitamin D with a higher risk of developing the disease. Hayes has been studying this “vitamin D hypothesis” for the past 25 years. She and her researchers have revealed some of the molecular mechanisms involved in vitamin D’s protective actions, and also explained how vitamin D interactions with estrogen may influence MS disease risk and progression in women.

In the current study, funded by the National Multiple Sclerosis Society, Hayes’ team compared various vitamin D–based treatments to standard MS drugs. In each case, vitamin D–based treatments won out. Mice that received them showed fewer physical symptoms and cellular signs of disease.

Hayes’ team compared the effectiveness of a single dose of calcitriol to that of a comparable dose of a glucocorticoid, a treatment now in use. Calcitriol came out ahead, inducing a nine-day remission in 92 percent of mice on average, versus a six-day remission in 58 percent for mice that received glucocorticoid.

“So, at least in the animal model, calcitriol is more effective than what’s being used in the clinic right now,” says Hayes.

But calcitriol can carry some strong side effects—it’s a “biological sledgehammer” that can raise blood calcium levels in people, Hayes says. After experimenting with various doses, her team arrived at a regimen of a single dose of calcitriol followed by ongoing vitamin D supplements in the diet. This one-two punch “was a runaway success,” she says. “One hundred percent of mice responded.”

While she is excited about the prospect of her research helping MS patients someday, Hayes is quick to point out that it’s based on a mouse model. The next step is human clinical trials. A multicenter clinical study is currently being designed. If trials are successful, people experiencing those first warning signs—the wobbly gait, the numb foot—could receive the new treatment and stop the disease in its tracks.

“It’s my hope that one day doctors will be able to say, ‘We’re going to give you an oral calcitriol dose and ramp up the vitamin D in your diet, and then we’re going to follow you closely over the next few months. You’re just going to have this one neurological episode and that will be the end of it,’” says Hayes. “That’s my dream.”

Targeting a Killer

By the time doctors diagnose septic shock, patients often are on a knife’s edge. At that point, for every hour that treatment is delayed, a person’s risk of death rises an alarming six percent.

Time is of the essence. And CALS animal sciences professor Mark Cook was part of a team that developed a breath biomarker technology capable of detecting septic shock 12 to 48 hours earlier than standard methods. This powerful device, which was patented in 2008 and is making its way through clinical trials, creates an exciting opportunity for new, life-saving medical interventions.

“If you can detect septic shock earlier, then you can begin to explore ways of treating it earlier,” says Cook, who already is in the process of developing a promising antibody-based treatment.

Septic shock—or severe sepsis—affects approximately 750,000 people in the United States each year, taking more than 200,000 lives and costing around $17 billion in treatment.

It occurs when a person’s immune system, spurred by a bacterial infection or serious physical trauma, launches a massive inflammatory response that can lead to a drop in blood pressure, multiple organ failure and death.

The gastrointestinal tract is believed to be the primary site of this runaway response. Because of that, some scientists call the gut “the motor for sepsis,” says Cook. So it’s no surprise that Cook looked to the gut for a solution.

With funding from a Robert Draper Technology Innovation Fund grant from the UW–Madison Graduate School, he began working to interfere with the activity of a protein called sPLA2, which is part of the chain of events in the gut that drives septic shock. It is a dual-purpose protein that can act as both an enzyme and a signaling molecule, so it wasn’t initially clear which of the protein’s roles—enzyme, signaling or both—were involved.

Cook and Jordan Sand, a scientist in Cook’s lab, decided to first try blocking the gut protein’s ability to signal, guessing that this would calm the immune response. So Sand made a series of antibodies that inhibited sPLA2’s signaling function—but not its enzyme function—and then tested them in a mouse model of septic shock.

“We actually made it much worse,” says Sand. “We absolutely failed. There’s no other way to say it.”

Sand went back and made antibodies that blocked only the protein’s enzyme function. Those worked. “We had 100 percent survival across the board,” says Sand.

If the antibody approach also works in people, this treatment could help patients with septic shock stay alive while they wait for antibiotics and other standard treatments to kick in.

Cook and Sand have filed a patent on the technology. But, Cook notes, “There are still a lot of steps to get this into human medicine.”

Tasty Solution

After having a stroke in 2008, Jan Blume lost the ability to swallow for two full years. As she slowly regained that vital function, she faced a new challenge: drinking the thickened beverages that are recommended for people with swallowing problems, or dysphagia. She found the drinks almost intolerable.

“They taste bad and the texture is so weird,” recalls Blume, a retired nurse living in Appleton who can now eat and drink whatever she wants. “At some point, I would have just stopped using them—and either done okay or developed problems.”

Fortunately there may soon be a better beverage option for people with swallowing problems, thanks to collaboration between a dysphagia specialist at the UW–Madison School of Medicine and Public Health—and a candy expert at CALS.

It started by chance when JoAnne Robbins, head of the medical school’s Swallowing, Speech and Dining Enhancement Program, asked CALS food scientist Rich Hartel if she could borrow his viscometer, a device that measures viscosity, or the thickness of fluids.

“After learning that one of Rich’s areas of expertise was chocolate, I mentioned that there are all these awful-tasting drinks made for people with swallowing problems, and nothing in chocolate,” recalls Robbins, a professor of medicine with an affiliate position in the CALS nutritional sciences department. “So we decided to develop a thickened chocolate drink together.”

The biomechanical events of swallowing are complex, involving 40 sets of muscles. Many things—including injury, illness and natural muscle atrophy due to aging—can cause dysphagia, which afflicts some 18 million adults in the United States.

The condition can be embarrassing. Some people with dysphagia simply stop going to restaurants or even eating with their families at home due to the struggle to swallow or the length of time it takes them to finish a meal. “This can have a devastating impact on social structures,” says Robbins.

But it’s more than just a quality-of-life issue, notes Robbins. Dysphagia can cause dehydration, hunger and malnutrition. Worse, if people with dysphagia aspirate liquids or food into their lungs, it can lead to pneumonia—and possibly death.

Many patients with dysphagia are advised to drink thickened beverages, which tend not to leak into the airway. But these products often leave much to be desired, and not just because of a bad flavor.

“The commercial products that are out there don’t match the diagnostic standards. So people think they’re buying a ‘nectar thick’ beverage, which is supposed to be a certain viscosity, but it’ll turn out that it’s not even close,” says Hartel.

That’s where Hartel and Robbins figured they could help: by developing what they call “bio-
physically based fluids” that match the diagnostic standards—making them safer for patients to drink—and that also taste good.

With the support of a U.S. Department of Agriculture grant, Hartel analyzed 15 thickeners and developed beverages using a handful of them. Robbins tested the drinks for safety in her patients, and a third team member, University of Minnesota researcher Zata Vickers, gathered key sensory data.

Ultimately the team gave up on chocolate after reading a number of studies showing that citrus flavors elicit a faster, better swallow. They are in the process of patenting their beverage technology through the Wisconsin Alumni Research Foundation, and are excited for the day when people who must drink thickened beverages—as Jan Blume did—will have a safer, tastier option.

“I’m in this to make my patients feel better,” says Robbins. Of her CALS collaborator Robbins says, “Rich is a very good partner. He was open to expanding the focus of his research program. He liked the idea of helping people directly.”

Field Notes: Potato Exchange Benefits Peruvians

In the growing region around Puno, Peru, farmers hedge their bets.

Located 12,000 feet above sea level, on the side of an Andean mountain, Puno has a growing season that’s short, cool and prone to frost. The staple food of the area is potato, and local farmers plant dozens of different varieties on their plots—some that they relish for their flavor, as well as some less palatable, frost-tolerant types.

In good years everything grows well and families have plenty to eat. In bad years—when there is an unseasonable or particularly hard frost—their preferred plants fail, and they must rely on the small, bitter potatoes produced by the hardy survivors.

Soon, however, they will have a better option. For the past two growing seasons, farmers near Puno and in three Peruvian highland villages have participated in a project to grow and test frost-tolerant versions of their favorite local varieties, with great success.

These special potato plants were developed in Wisconsin by a team of CALS plant scientists and plant breeders using germplasm stored in the U.S. Potato Genebank, located in Sturgeon Bay.

“I think this is the first case where a potato developed in the U.S. has been accepted by local farmers in these communities in the Andes,” says project coordinator Alfonso del Rio, an associate scientist in the lab of John Bamberg. As an employee of the USDA’s Agricultural Research Service, Bamberg serves as director of the U.S. Potato Genebank. He is also a professor of horticulture with CALS.

The plant materials used for the project, like the vast majority found in the U.S. Potato Genebank, were brought to the United States from the Andes, the potato’s site of origin. This makes the project a special opportunity for potato breeders in the United States to give something back.

“We’re interested in returning the benefits of our genebank to Peru and the broader Andean region because that’s the area that supplied our country with germplasm,” says Bamberg, who led the project’s breeding effort. Earlier work by CALS horticulture professor Jiwan Palta, the third member of the team, made modern marker-assisted breeding for frost tolerance possible.

To make the new potato lines, Bamberg took an exceptionally frost-tolerant wild relative of the potato family—a weed, basically—and crossed it with seven popular native Peruvian potato varieties to generate frost-tolerant versions of the native potato plants.

Although the new potato lines were originally meant to be added to Peru’s national potato breeding program as germplasm for further breeding, the farmers who were involved in the trials are eager to start growing some of them right away. And no wonder. This past growing season in Puno, after a late, hard frost, a few of the new frost-tolerant lines far outperformed the local varieties, yielding twice as many pounds of potato per plot.

The CALS team hopes these more dependable potato plants will help bolster Peru’s vulnerable rural communities.

“If the farmers could send part of their harvest to market, even 10 or 20 percent, they could have some money to invest in community development—in things like clinics, schools and libraries,” says del Rio.